Hematological abnormalities in HIV-antiretroviral therapy naïve clients as seen at an immune suppression syndrome clinic at Mbarara Regional Referral Hospital, southwestern Uganda.

AIM/OBJECTIVE: To assess the common hematological abnormalities among HIV-antiretroviral therapy (ART) naïve clients attending an immune suppression syndrome (ISS) clinic at Mbarara Regional Referral Hospital (MRRH), southwestern Uganda. PATIENTS AND METHODS: This was a cross-sectional study carried out during the months of March to August 2016 at the ISS clinic of MRRH. We collected approximately 4.0 mL of EDTA anticoagulated blood samples, which were assayed for complete blood count, CD4+ cell count and thin film examination. Correlation of the hematological abnormalities with CD4+ cell counts was done using correlation coefficient (r) and analysis of variance (F), and the p-value was set at ≤0.05. RESULTS: A total of 141 clients were enrolled. Of these, 67.38% (95/141) were anemic, 26.24% (40/141) had thrombocytopenia while 26.95% (38/141) had leucopenia. Of the 95 participants with anemia, 89.47% (85/95) presented with normocytic-normochromic anemia, 8.42% (8/95) with microcytic-hypochromic anemia and 2.11% (2/95) with macrocytic-hypochromic anemia. Anemia was not different across the several World Health Organization (WHO) stages of HIV infection disease progression (p>0.05). Statistically significant differences were present among participants with leucopenia (p<0.05). Also, leucopenia was more prevalent (11/38) among participants in WHO stage 4 of HIV infection. CD4+ cell counts correlated with thrombocytopenia (r=0.24, p<0.05) and leucopenia (r=0.15, p<0.05). CONCLUSION: People living with HIV/AIDS (PLWHIV/AIDS) ought to be routinely monitored and treated for the occurrence of hematological abnormalities. Early initiation of ART can help to prevent some hematological abnormalities.

Toxicity of Amphotericin B Deoxycholate-Based Induction Therapy in Patients with HIV-Associated Cryptococcal Meningitis.

Amphotericin B deoxycholate (AmBd) is the recommended induction treatment for HIV-associated cryptococcal meningitis (CM). Its use is hampered by toxicities that include electrolyte abnormalities, nephrotoxicity, and anemia. Protocols to minimize toxicity are applied inconsistently. In a clinical trial cohort of AmBd-based CM induction treatment, a standardized protocol of preemptive hydration and electrolyte supplementation was applied. Changes in blood counts, electrolyte levels, and creatinine levels over 14 days were analyzed in relation to the AmBd dose, treatment duration (short course of 5 to 7 days or standard course of 14 days), addition of flucytosine (5FC), and outcome. In the 368 patients studied, the hemoglobin levels dropped by a mean of 1.5 g/dl (95% confidence interval [CI], 1.0 to 1.9 g/dl) following 7 days of AmBd and by a mean of 2.3 g/dl (95% CI, 1.1 to 3.6 g/dl) after 14 days. Serum creatinine levels increased by 37 µmol/liter (95% CI, 30 to 45 µmol/liter) by day 7 and by 49 µmol/liter (95% CI, 35 to 64µmol/liter) by day 14 of AmBd treatment. Overall, 33% of patients developed grade III/IV anemia, 5.6% developed grade III hypokalemia, 9.5% had creatinine levels that exceeded 220 µmol, and 6% discontinued AmBd prematurely. The addition of 5FC was associated with a slight increase in anemia but not neutropenia. Laboratory abnormalities stabilized or reversed during the second week in patients on short-course induction. Grade III/IV anemia (adjusted odds ratio [aOR], 2.2; 95% CI, 1.1 to 4.3; P = 0.028) and nephrotoxicity (aOR, 4.5; 95% CI, 1.8 to 11; P = 0.001) were risk factors for 10-week mortality. In summary, routine intravenous saline hydration and preemptive electrolyte replacement during AmBd-based induction regimens for HIV-associated CM minimized the incidence of hypokalemia and nephrotoxicity. Anemia remained a concerning adverse effect. The addition of flucytosine was not associated with increased neutropenia. Shorter AmBd courses were less toxic, with rapid reversibility.

No association found between traditional healer use and delayed antiretroviral initiation in rural Uganda.

Traditional healer and/or spiritual counselor (TH/SC) use has been associated with delays in HIV testing. We examined HIV-infected individuals in southwestern Uganda to test the hypothesis that TH/SC use was also associated with lower CD4 counts at antiretroviral therapy (ART) initiation. Approximately 450 individuals initiating ART through an HIV/AIDS clinic at the Mbarara University of Science and Technology (MUST) were recruited to participate. Patients were predominantly female, ranged in age from 18 to 75, and had a median CD4 count of 130. TH/SC use was not associated with lower CD4 cell count, but age and quality-of-life physical health summary score were associated with CD4 cell count at initiation while asset index was negatively associated with CD4 count at ART initiation. These findings suggest that TH/SC use does not delay initiation of ART.

Short course amphotericin B with high dose fluconazole for HIV-associated cryptococcal meningitis.

OBJECTIVE: To define more rapidly effective initial antifungal regimens sustainable in resource-constrained settings. METHODS: Cohort study in SW Uganda: Thirty HIV-seropositive, antiretroviral therapy-naïve, patients with first episode cryptococcal meningitis were treated with high dose fluconazole (1200 mg/d for 2 weeks, then 800 mg/d until ART started) plus amphotericin B (AmB, 1 mg/kg/d), with routine normal saline and potassium supplementation, for the initial 5 days. Outcome measures were early fungicidal activity (EFA), determined by serial quantitative CSF cultures, safety, and mortality. RESULTS: EFA was -0.30 ± 0.11 log CFU/day calculated over the first 2 weeks of treatment, with no reduction in the rate of clearance between days 5 and 14. There was no grade IV hypokalemia or elevated creatinine, and no grade III or IV anemia or elevation of ALT. AmB or high dose fluconazole were not stopped early in any patient. Mortality was 23% at 2, and 28% at 10 weeks. CONCLUSIONS: Short course AmB was associated with rapid clearance of infection and was well-tolerated, suggesting it could be used safely in many centres currently relying on fluconazole monotherapy. Phase III trials are needed in African centres to compare short course with the standard 2-week course of AmB.